Summary of work: Recently, it was demonstrated (Prashad et al.) that cells from patients with familial Alzheimer disease (AD) had an altered response to fluorescent light (FL) exposure as compared to cells from unaffected individuals, suggesting that there may be some deficiency in the DNA repair processing of oxidative lesions induced by FL in AD. This project was initiated to develop a better understanding of the DNA repair capacity of AD for FL induced lesions. The formation and repair of oxidative base lesions in AD and normal fibroblasts was measured after exposure to FL using gas chromatography/mass spectrometry (GC/MS) analysis. Several oxidative DNA lesions were induced in AD and normal cells by exposure to FL. The oxidative lesions induced by FL exposure include 5-hydroxycytosine, formamidopyrimidine, and 8-hydroxy guanine. Additionally, the capacity of AD cells to repair oxidative DNA damage is being investigated using an in vitro DNA repair synthesis assay. In vitro DNA repair synthesis was carried out by whole cell extracts from AD and normal cells on plasmid DNA damaged by gamma-irradiation. This substrate was repaired efficiently by whole cell extracts from both AD and normal cells. Similar in vitro assays using plasmid DNA damaged by various oxidative sources are currently in progress.